1. The document discusses acute coronary syndrome and its pathophysiology including plaque rupture and thrombosis leading to dynamic obstruction. 2. It summarizes several studies on outcomes of invasive versus conservative treatment strategies for acute coronary syndrome patients, finding reduced mortality and myocardial infarction with invasive approaches. 3. Biomarkers like troponin and homocysteine are discussed as risk factors for adverse outcomes in acute coronary syndrome.

1. ACUTE CORONARY SYNDROME

7. TROPONIN T LEVELS IN ACS & CARDIAC DEATH 1506 Patients FRISC – Circ. 1996, 93 : 1651

8. TACTICS – TIMI 18 New Eng. J. Med, 2001, 344 : 1879 21 % risk reduction (p=0.048) 36 % risk reduction (p=0.018)

14. 100 80 60 40 20 0 (n=895) (n=915) (n=856) (n=873) (n=799) (n=814) Intervention Conservative Intervention Conservative Intervention Conservative Proportion of patients (%) Baseline 4 months 1 year Prevalence of angina over time treatment Lancet 2002,360,743 Grade 1 Grade 2 Grade 3/4

15. Nitricoxide (NO) Thrombomodulin TM Protects Endothelium Endothelium Damages Endothelium Depletion of NO and TM Reactive Oxygen Species Oxidation Homocysteine Mechanism of Homocysteine Induced Vascular Damage

19. ASSESSMENT OF THE CLINICAL UTILITY OF NOVEL MARKERS OF CARDIOVASCULAR RISK ADDITIVE TO TOTAL AND ASSAY PROSPECTIVE HIGH-DENSITY CONDITIONS STUDIES LIPOPROTEIN MARKER STANDARDIZED ? CONSISTENT ? CHOLESTEROL ? Lipoprotein (a) No Yes/no Yes /no Total homocysteine Yes Yes/no Yes /no Tissue-type plasminogen activator Yes/no Yes Yes/no And plasminogen activator inhibitor Fibrinogen Yes/no Yes Yes High-sensitiviety-C-reactive protein Yes Yes Yes From Ridker PM: Evaluating novel cardiovascular risk factors : Can we better predict heart attacks ?Ann Intern Med 130:933-937,1999

20. 100 80 60 40 20 0 (n=895) (n=915) (n=856) (n=873) (n=799) (n=814) Intervention Conservative Intervention Conservative Intervention Conservative Proportion of patients (%) Baseline 4 months 1 year Prevalence of angina over time treatment Lancet 2002,360,743 Grade 1 Grade 2 Grade 3/4

26. Association between angiotensin-converting enzyme (ACE) genotypes and incidence of myocardial infarction in men with primary hypercholesteolemia 100 90 80 70 60 50 40 30 20 10 0 40 45 50 55 60 65 Incidence of Myocardial Infarction (%) Age (years) DI + II DD

27. CAD – INFECTION Circ. 2002, 105, 1555 Patients randomized (n=152) Patients commencing treatment (n = 148) Placebo (n=74) Clarithromycin (n=74) Urgent revascularization (n=2) Pancreatitis (n = 1) Renal failure (n=1)

28. Kaplan-Meier plot of cumulative survival during follow-up Circ. 2002, 105, 1555

30. Hyperhomocysteinemia and risk of atherosclerotic vascular disease Meta analysis of 27 studies * P < 0.05 v/s normal (Boushey et al) * * *

31. Homocysteine levels in CAD patients and controls A Higher plasma homocysteine levels in Indian patients with CAD B Increased risk in CAD in Indian Asians due to hyperhomocysteinemia 1.5 1.4 1.3 1.2 1.1 1.0 11-12 12-1 113-1 14-15 >=15 Odds ratio for CHD Homocysteine conc. (micrommol/L) *p<0.05 n=775 * 1.07 1.15 1.24 1.33 1.43

34. Joint effects of antimicrobial antibodies, smoking and CRP on the risk of coronary events

35. HOMOCYSTEINE METABOLISM

39. Antman RM et al JAMA 2000, 284, 835 % Population 4.3 17.3 32.0 29.3 13.0 3.4 6-7 SABATINE AND ANTMAN TIMI RISK SCORE FOR UA/NSTEMI